Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The characteristics of vasopressin-stimulated phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P2) and phosphatidylcholine (PtdCh) hydrolysis were examined in A10 vascular smooth muscle cells (VSMC), by assessing the formation of [3H]-inositol phosphates ([3H]-IP) and the accumulation of the phospholipase D (PLD) specific product, [3H]-phosphatidylbutanol ([3H]-PtdBuOH). 2. Vasopressin ([Arg8]-VP) and a number of related analogues stimulated the accumulation of [3H]-IP and [3H]-PtdBuOH with similar EC50 values, generating the same rank order of potency for each response (Arg8-VP = vasotocin = Lys8-VP much greater than oxytocin). 3. Inhibition of vasopressin-stimulated [3H]-IP and [3H]-PtdBuOH accumulation by the V1a receptor antagonists, Des-Gly9[beta-mercapto-beta,beta,-cyclopentamethylene propionyl, O-Et-Tyr2,Val4,Arg8]-vasopressin generated similar IC50 values suggesting that both these responses are mediated through the activation of a single V1a receptor subtype. 4. The onset of vasopressin-stimulated inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) mass formation preceded [3H]-PtdBuOH accumulation indicating that PtdCh hydrolysis was activated subsequent to PtdIns(4,5)P2 breakdown. 5. The protein kinase C (PKC) activator, tetradecanoylphorbol acetate (TPA) also stimulated [3H]-PtdBuOH accumulation. Preincubation with the PKC inhibitor Ro-31-8220 abolished both TPA- and vasopressin-stimulated [3H]-PtdBuOH, suggesting that the intermediate activation of protein kinase C is involved in the regulation of PLD by vasopressin. 6. Pretreatment of the A10 VSMC with Ro-31-8220 (100 microM) also potentiated vasopressin-stimulated Ins(1,4,5)P3 mass formation.Therefore stimulation of PKC may have opposing roles in the regulation of agonist activation of PLC and PLD.7. Preincubation of the cells with EGTA, verapamil, or the receptor-operated calcium channel antagonist, SK&F 96365, reduced vasopressin-stimulated [3H]-PtdBuOH accumulation by approximately 30%, suggesting that influx of calcium has a significant role to play in the regulation of vasopressinstimulated PLD activity.
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PMID:Vasopressin-stimulated [3H]-inositol phosphate and [3H]-phosphatidylbutanol accumulation in A10 vascular smooth muscle cells. 133 Jan 54

In the guinea pig myometrium, carbachol, oxytocin, and fluoroaluminates stimulated the breakdown of phosphatidylinositol 4,5-bisphosphate, which was insensitive to pertussis toxin [Biochem. J. 255:705-713 (1988)]. We now demonstrate that an increased accumulation of inositol phosphates, with an early production of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], could also be obtained with K+ (30 mM) and the Ca2+ ionophore ionomycin. Removal of extracellular Ca2+ or addition of the Ca2+ channel antagonists nifedipine and verapamil almost totally abolished stimulations elicited by high K+ and partially attenuated receptor- and fluoroaluminate-mediated increases in inositol phosphates. Isoproterenol similarly attenuated the accumulation of inositol phosphates elicited by carbachol, oxytocin, and fluoroaluminates (maximal inhibition, 35%; EC50, 0.5 nM), with no change in the rate of Ins(1,4,5)P3, inositol bisphosphate, and inositol monophosphate generation. The beta-adrenergic receptor-induced inhibition was prevented by pertussis toxin and could not be reproduced by forskolin, indicating that cAMP was not involved. Experimental findings were, rather, consistent with a predominant role for Ca2+. Thus, inhibition due to isoproterenol was lost in a Ca(2+)-depleted medium and was not additive with that caused by nifedipine. Accumulation of inositol phosphates triggered by high K+ was insensitive to the beta-adrenergic receptor inhibition. The inhibitory effect of isoproterenol, similar to that of nifedipine, was counteracted by ionomycin and also by the Ca2+ channel agonist Bay K 8644. These data indicate that in the myometrium 1) phospholipase C can be activated through a voltage-gated Ca2+ entry-dependent process that contributes at least partially to the stimulations triggered by receptor- and/or guanine nucleotide-binding protein-mediated activation and 2) beta-adrenergic receptor activation is linked via a cAMP-independent, pertussis toxin-sensitive pathway to an inhibition of voltage-gated Ca2+ channels, resulting in an attenuation of the Ca(2+)-associated generation of inositol phosphates.
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PMID:Activation of beta-adrenergic receptors inhibits Ca2+ entry-mediated generation of inositol phosphates in the guinea pig myometrium, a cyclic AMP-independent event. 137 85

The phospholipase C (PLC)-activating gonadotrophin-releasing hormone (GnRH) receptor is thought not to rapidly desensitise in alphaT3-1 cells. This extremely unusual characteristic raises the concern that it might be a feature of the cell type, rather than the receptor per se. Here we have used video imaging to establish whether the effects of endogenous PLC-activating G-protein coupled receptors (GPCRs) on Ca2+ ion concentration [Ca2+]i desensitise in these cells. Oxytocin, endothelin-1, methacholine, and UTP all caused [Ca2+]i increases which underwent rapid homologous desensitisation in that they were transient and responses to repeat stimuli were attenuated whereas subsequent responses to GnRH were not. To test whether receptor reserve obscures functional desensitisation of GnRH receptors, a photoaffinity antagonist (Pant-1), was used to effect a partial and irreversible receptor blockade. UV crosslinking in medium with 1000 nM Pant-1 reduced GnRH receptor number to 20 +/- 5% and reduced maximal buserelin-stimulated [3H]IP(X) accumulation to 57 +/- 5%, demonstrating removal of receptor reserve. In control alphaT3-1 cells the initial rate of GnRH-stimulated [3H]IP(X) accumulation was maintained for at least 5 min and GnRH caused a sustained increase in Ins(1,4,5)P3 mass (confirming the resistance of GnRH receptors to desensitisation) and Pant-1 pre-treatment reduced the magnitude of these responses without altering their temporal profiles. In alphaT3-1 cells stably transfected with recombinant human muscarinic receptors (alphaT3-1/M3), responses to methacholine were characteristic of desensitising GPCRs (transient Ins(1,4,5)P3 and curvilinear [3H]IP(X) responses) and were unaltered by Pant-1. To test the relevance of phospholipid pool size, alphaT3-1/M3 cells were pre-treated with GnRH or methacholine in medium with LiCl (to deplete PtdIns(4,5)P2 pools). These pre-treatments reduced subsequent responses to methacholine and GnRH comparably, indicating access to a shared PtdIns(4,5)P2 pool. Partial depletion of this pool (GnRH pre-treatment in medium with LiCl) reduced the magnitude of the [3H]IP(X) and Ins(1,4,5)P3 responses to methacholine and GnRH, without altering their temporal profiles. Thus the GnRH receptor does not undergo rapid homologous desensitisation in alphaT3-1 cells in spite of the fact that they can desensitise other endogenous (and recombinant) PLC-activating GPCRs, and the lack of desensitisation cannot be attributed to the existence of GnRH receptor reserve or access to an atypically large or rapidly re-cycled PtdIns(4,5)P2 pool. This unique functional characteristic (mammalian GnRH receptors are the only PLC-activating GPCRs known not to rapidly desensitise) almost certainly therefore reflects the atypical structure of these receptors (mammalian GnRH receptors are the only PLC-activating GPCRs known to lack C-terminal tails).
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PMID:The lack of gonadotrophin-releasing hormone (GnRH) receptor desensitisation in alphaT3-1 cells is not due to GnRH receptor reserve or phosphatidylinositol 4,5-bis-phosphate pool size. 1019 3